Salivary excretion of 5-fluorouracil. I. Fluctuation of the saliva/plasma concentration ratio and salivary clearance in beagle dogs following bolus intravenous administration.

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Abstract
Salivary excretion of 5-fluorouracil (5-FU) [an antineoplastic drug] was investigated following bolus i.v. administration (20 mg/kg) in 4 beagle dogs. Parotid (Pr) and mandibular-sublingual saliva (MS) were collected separately by stimulating salivation with 10% citric acid. Significant correlations were observed between 5-FU concentrations in plasma and in each saliva (P < 0.01). The saliva/plasma drug concentration ratios (S/P ratios) showed fairly large fluctuations (0.472 .+-. 0.0303 for Pr, 0.200 .+-. 0.196 for MS) and were not influenced by protein concentration in saliva or salivary flow rate. The observed S/P ratios were significantly different from the S/P ratios calculated by the use of Matin''s equation which employed the observed salivary pH values and free fraction of 5-FU in plasma and saliva (P < 0.001). The salivary excretion of 5-FU cannot be explained by pH-partition theory. Total salivary clearance of 5-FU (0.123 .+-. 0.093 ml/min per kg) was < 0.5% of total body clearance. In each saliva, clearance of 5-FU was almost independent of salivary flow rate. The relationship between salivary clearance and plasma 5-FU concentration is discussed.